Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18

Chien liang Glenn Lin, Irina Orlov, Alicia M. Rugglero, Margaret Dykes-Heberg, Andy Lee, Mandy Jackson, Jeffrey D. Rothstein

Research output: Contribution to journalLetterpeer-review

191 Scopus citations


Excitatory amino-acid carrier 1 (EAAC1) is a high-affinity Na+-dependent L-glutamate/D, L-aspartate cell-membrane transport protein. It is expressed in brain as well as several non-nervous tissues. In brain, EAAC1 is the primary neuronal glutamate transporter. It has a polarized distribution in cells and mainly functions perisynaptically to transport glutamate from the extracellular environment. In the kidney it is involved in renal acidic amino-acid re-absorption and amino-acid metabolism. Here we describe the identification and characterization of an EAAC1-associated protein, GTRAP3-18. Like EAAC1, GTRAP3-18 is expressed in numerous tissues. It localizes to the cell membrane and cytoplasm, and specifically interacts with carboxy-terminal intracellular domain of EAAC1. Increasing the expression of GTRAP3-18 in cells reduces EAAC1-mediated glutamate transport by lowering substrate affinity. The expression of GTRAP3-18 can be upregulated by retinoic acid, which results in a specific reduction of EAAC1-mediated glutamate transport. These studies show that glutamate transport proteins can be regulated potently and that GTRAP can modulate the transport functions ascribed to EAAC1. GTRAP3-18 may be important in regulating the metabolic function of EAAC1.

Original languageEnglish (US)
Pages (from-to)84-88
Number of pages5
Issue number6824
StatePublished - Mar 2001

ASJC Scopus subject areas

  • General


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